This is a competing renewal application for a K24 in patient-oriented research (POR) for Silva Arslanian, M.D. of the Children's Hospital University of Pittsburgh, School of Medicine. The applicant's original award provided support for POR for investigating insulin resistance during childhood growth and development, mentoring of junior faculty and fellows, advancing the research in new directions, and leadership in POR locally, nationally, and internationally. All of these aims have been executed with outstanding rigor, and the candidate has been successful in accomplishing the following: 1) Competitively renewed her R01 (2R01 HD027503); 2) Obtained new independent NIH funding as PI (1U01 DK063704), and funding for several pharmaceutical trials; 3) Advanced her mentoring commitment by obtaining new funding as PI for a felllow training grant (T32 DK63686) and junior faculty development grant (K12 DK63704), both in pediatric diabetes; 4) Established new collaborations in POR at her own institution (1R01- HD38425, and 5U01 DK061230; PI, Marsha Marcus, Ph.D.) and with other academic institutions (1R01 DK071485; PI, Shumei Sun, Ph.D., Wright State University); 5) Competitively renewed the GCRC grant (5M01RR00084), with an outstanding score, at Children's Hospital of Pittsburgh, where she is director; 6) Became a board member of the Endocrine Fellows Foundation, a national organization whose primary and sole mission is the education and research support of endocrine fellows nationally; 7) Increased the pool of pediatrician investigators in POR by attracting and mentoring new fellows/faculty from within and outside the institution; 9) Assumed a leadership role in directing the newly founded Weight Management & Wellness Center (WMWC) at Children's Hospital of Pittsburgh; and, last but not least, received the inaugural University of Pittsburgh Medical Center Richard L. Day Endowed Chair in Pediatrics. This renewal application proposes to: 1) Continue the leadership of the PI in POR in the area of childhood obesity, insulin resistance, type 2 diabetes, and cardiovascular disease, major public health problems of this millennium; 2) Provide ongoing mentoring to junior faculty, fellows, and medical students; and 3) To conduct innovative research in childhood insulin resistance, its causes, complications and control strategies. Support for these activities will enable Dr. Arslanian to further strengthen and expand the research scope of childhood obesity and insulin resistance but, more importantly, contribute to the academic development of young and upcoming clinician-investigators who will contribute to the global childhood obesity control by developing new paradigms of intervention, prevention and treatment.